Abstract

Background

Pain tolerance is subject to considerable inter-individual variation, which may be
influenced by a number of genetic and non-genetic factors. The mu, delta and kappa
opioid receptors play a role in pain perception and are thought to mediate different
pain modalities. The aim of this study was to explore associations between pain thresholds
and gender and genetic variants in the three opioid receptor genes (OPRM, OPRD and OPRK). Experimental multi-modal pain data from previously published studies carried out
in healthy Caucasian volunteers were used in order to limit the number of confounders
to the study outcome. Data on thermal skin pain (n=36), muscle pressure pain (n=31)
and mechanical visceral pain (n=50)) tolerance thresholds were included.

Results

Nineteen genetic polymorphisms were included in linear regression modeling. Males
were found to tolerate higher thermal and muscle pressure pain than females (p=0.003
and 0.02). Thirty four percent of variability in thermal skin pain was accounted for
by a model consisting of OPRK rs6473799 and gender. This finding was just outside significance when correction for multiple
testing was applied. Variability in muscle pressure pain tolerance was associated
with OPRK rs7016778 and rs7824175. These SNPs accounted for 43% of variability in muscle pressure pain sensitivity
and these findings remained significant after adjustment for multiple testing. No
association was found with mechanical visceral pain.

Conclusion

This is a preliminary and hypothesis generating study due to the relatively small
study size. However, significant association between the opioid receptor genes and
experimental pain sensitivity supports the influence of genetic variability in pain
perception. These findings may be used to generate hypotheses for testing in larger
clinical trials of patients with painful conditions.